7ZDD
Crystal structure of TRIM33 PHD-Bromodomain isoform B in complex with H3K10ac histone peptide.
Summary for 7ZDD
| Entry DOI | 10.2210/pdb7zdd/pdb |
| Related | 5MR8 |
| Descriptor | E3 ubiquitin-protein ligase TRIM33, Histone H3.X, 1,2-ETHANEDIOL, ... (5 entities in total) |
| Functional Keywords | e3 ubiquitin-protein ligase, acetylation, transcription |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 23828.29 |
| Authors | Caria, S.,Duclos, S.,Crespillo, S.,Errey, J.,Barker, J.J. (deposition date: 2022-03-29, release date: 2022-06-29, Last modification date: 2024-11-13) |
| Primary citation | Sekirnik, A.R.,Reynolds, J.K.,See, L.,Bluck, J.P.,Scorah, A.R.,Tallant, C.,Lee, B.,Leszczynska, K.B.,Grimley, R.L.,Storer, R.I.,Malattia, M.,Crespillo, S.,Caria, S.,Duclos, S.,Hammond, E.M.,Knapp, S.,Morris, G.M.,Duarte, F.,Biggin, P.C.,Conway, S.J. Identification of Histone Peptide Binding Specificity and Small-Molecule Ligands for the TRIM33 alpha and TRIM33 beta Bromodomains. Acs Chem.Biol., 17:2753-2768, 2022 Cited by PubMed Abstract: TRIM33 is a member of the tripartite motif (TRIM) family of proteins, some of which possess E3 ligase activity and are involved in the ubiquitin-dependent degradation of proteins. Four of the TRIM family proteins, TRIM24 (TIF1α), TRIM28 (TIF1β), TRIM33 (TIF1γ) and TRIM66, contain C-terminal plant homeodomain (PHD) and bromodomain (BRD) modules, which bind to methylated lysine (KMe) and acetylated lysine (KAc), respectively. Here we investigate the differences between the two isoforms of TRIM33, TRIM33α and TRIM33β, using structural and biophysical approaches. We show that the N1039 residue, which is equivalent to N140 in BRD4(1) and which is conserved in most BRDs, has a different orientation in each isoform. In TRIM33β, this residue coordinates KAc, but this is not the case in TRIM33α. Despite these differences, both isoforms show similar affinities for H3K18Ac, and bind preferentially to H3K9MeK18Ac. We used this information to develop an AlphaScreen assay, with which we have identified four new ligands for the TRIM33 PHD-BRD cassette. These findings provide fundamental new information regarding which histone marks are recognized by both isoforms of TRIM33 and suggest starting points for the development of chemical probes to investigate the cellular function of TRIM33. PubMed: 36098557DOI: 10.1021/acschembio.2c00266 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.625 Å) |
Structure validation
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